The oxidative stress and inflammatory environment trigger an unhealthy circle, which can lead to various inflammatory diseases. Ipomoea pes-caprae, a traditional medicine mangrove plant, posed many pharmacological activities, including antioxidant, anti-inflammatory and anticancer effects. However, the possible mechanisms involved in Ipomoea pes-caprae are still unclear. This study aimed to investigate the antioxidant and anti-inflammatory effects of different solvent extracts from Ipomoea pes-caprae on lipopolysaccharide (LPS) stimulated macrophages. Three different solvent gradients were prepared orderly from non-polar to polar: hexane (Hex), supercritical fluid extraction using carbon dioxide plus EtOH as co-solvent (SCO2) and ethanol (EtOH). All 3 extracts were screened for the cytotoxicity on RAW264.7 cells by MTT assay. The non-toxic doses were investigated for reactive oxygen species (ROS) scavenging by DPPH and DCFH-DA assays and evaluated their anti-inflammatory activities via inhibition against LPS-induced nitric oxide (NO), prostaglandin E2 (PGE2), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression. All 3 extracts (25 - 50 μg/mL) exhibited DPPH scavenging and reduced intracellular ROS level in the order of SCO2 > EtOH > Hex. Further, these extracts suppressed NO and PGE2 production by regulating iNOS and COX-2 mRNA expression in the order of SCO2 > Hex > EtOH. Additionally, their inhibitory effects were in a similar pattern as the standard drugs L-NAME and celecoxib. These findings support the traditional use of Ipomoea pes-caprae in treating inflammatory diseases due to its attenuation of inflammation in activated macrophage. Also, a wide range of secondary metabolites in unique ecology may be useful as one of the alternative therapies for inflammatory diseases.
 HIGHLIGHTS
 
 Ipomoea pes-caprae employ a sort of secondary metabolites under stressful high salt conditions with benefit for new drug discoveries
 SCO2 extract exhibited the strongest activities in the LPS-induced ROS and PGE2 production
 These bioactive compounds contained in Ipomoea pes-caprae confirm the traditional use against jellyfish stings and may targeting inflammatory pathways
 
 GRAPHICAL ABSTRACT